Recently, calcium-independent enhancement of cardiac contractility by adrenergic agents has been reported. alpha stimulation increases actomyosin ATPase rate and force in muscles with V3, but not V1, isomyosin; the mechanism(s) are unknown. Beta stimulation increases force and actomyosin ATPase rate in muscles with V1, but not V3, isomyosin, and increases crossbridge cycling rate in muscles with V3 isomyosin; the effect on cycling rate in muscles with V1 isomyosin is uncertain. These effects may involve the second messenger cAMP; details are unknown at present. The effect of alpha stimulation on cycling rate has not yet been tested. These observations raise the intriguing possibility that adrenergic agents selectively affect the different isoforms of cardiac myosin, providing a subtle mechanism for modulating cardiac contractility. Driven by these exciting new possibilities, the long term objective of this research is to further probe the mechanism (s) by which cardiac contractility is fine- tuned by the influence of adrenergic stimuli on crossbridge cycling kinetics. The specific aims are to 1) determine if beta adrenergic stimulation increases crossbridge cycling rate in muscles containing primarily the V1 isoenzyme of myosin, 2) determine if elevated intracellular cyclic AMP, an element of the second messenger cascade initiated by beta adrenergic stimulation, is factor in the increase in crossbridge cycling rate in muscle containing mostly the V3 isoenzyme of myosin and 3) determine if alpha adrenergic stimulation, analogous to the effects of beta adrenergic stimulation, alters crossbridge cycling rate in muscle containing either mostly the V1 or mostly the V3 isomyosin. Small amplitude sinusoidal length oscillations, at each of 50 discrete frequencies, will be applied to isometrically contracting right ventricular papillary muscles. At each frequency stiffness will be evaluated as the ratio of (oscillatory) force to length. Crossbridge cycling rate will be gauged from the frequency at which stiffness amplitude exhibits a minimum. In addition to expanding our understanding of the manifold ways in which cardiac contractility is regulated, these studies may uncover a mechanism of action of the newer cardiotonic bipyridine derivatives which raises cAMP and may thereby modulate the kinetics of the cyclical interaction of myosin with actin-the fundamental force generator in the heart.